Lung cancer targeted therapy trend: Teresa is becoming home run king ds-8201, leading innovation and breakthrough

At the beginning of June 2020, the ASCO meeting endedIn the above, the author initially introduced the important progress of tumor immunity under lung cancer indications in this meeting, among which the first disclosed clinical data of tigit monoclonal antibody tiragolumab attracted much attentionIn this paper, we hope to summarize several drugs that are worthy of attention under the driving gene mutation of lung cancer< br / > since 1997, the world's first clinical trial of EGFR inhibitors has been launchedIn the field of lung cancer targeted chemotherapy for more than 20 years, 1Targeted therapies such as EGFR, ALK and ros1 have been emerging, which have brought benefits to non-small cell lung cancer patients with different fine-grained stratification; 2New targeted chemotherapy schemes such as RET and c-Met have also been emerging, This is also improving the survival of specific lung cancer patients; 3The new generation of targeted chemotherapy program is also improving the quality of life of patients with drug-resistant mutations; 4The identification of new targeted gene mutations determines the breakthrough basis of targeted chemotherapy in the future< br / > < br / > < br / > on November 13, 2015, the first EGFR T790M mutation targeted chemotherapy scheme, Teresa (oxitinib), was approved for marketing in the United StatesThe new generation of targeted chemotherapy scheme is improving the quality of life of drug-resistant mutation patients, which is a milestone progress! < br / > 1On November 13, 2015, for the first time in the world, Teresa (ositini) approved the indication of EGFR T790M mutant non-small cell lung cancer patients, which has been approved in 46 countries around the world; < br / > 2On April 18, 2018, Teresa (ositini) received a first-line treatment, and the indication of EGFR exon 19 del / exon 21 L858R mutant non-small cell lung cancer patients, EGFR exon 19 del / exon 21 L858R mutation is the two most common mutations in patients with non-small cell lung cancer, and has been approved in 20 countries around the world; < br / > so far, ositinib has successfully covered most patients with advanced EGFR mutation in non-small cell lung cancer, becoming the standard therapy for patients with stage IV EGFR / EGFR T790M mutationEGFR exon 20 ins patients are still breaking through, but there is not much hope< br / > early lung cancer (stage I / II / III) must be an important development direction of oxitinib in the next stage, which is also the key to determine the market value of oxitinib< br / > at the ASCO meeting in 2020, oshitinib announced a major breakthroughThe data of adaura (nct0251106) showed that oshitinib vs placebo could significantly prolong the disease-free survival period of patients with stage II / IIIA non-small cell lung cancer, DFS 90% vs 34%, HR 0.17 in two years < br / > adaura trial protocol: < br / > < br / > < br / > adaura significantly prolonged the disease-free survival of patients with stage II / IIIa < br / > < br / > < br / > adaura significantly prolonged the disease-free survival of patients with stage Ib / II / IIIa < br / > < br / > < br / > < br / > the success of adaura is an important breakthrough, and ohitinib has become the first EGFR targeted therapy that can bring clinical benefits to patients with early lung cancer! Adaura will obviously expand the clinical benefit population of oshitinib, and the way of oshitinib's gorgeous upgrading will be more and more smooth In the future, the directions worthy of attention for oxitinib are as follows: < br / > 1 In patients with stage IV EGFR / EGFR T790M mutation, oxitinib is expanding the combination therapy and continues to expand the clinical benefits for patients; < br / > 2 In patients with stage I / II / III non-small cell lung cancer, oxitinib is expanding the beneficiary population Adaura, neoadaura and Laura are three clinical trials worthy of attention In the middle of 1980s, it was found for the first time that the mutation of c-met was associated with lung cancer In the following years, it was gradually clarified that the rearrangement, amplification, mutation and up-regulation of c-met gene were associated with the clinical benefits of lung cancer patients In general, there are three common forms of HGF / c-Met signaling pathway abnormalities: 1 C-met rearrangement, mutation and amplification; 2 Overexpression of c-met protein; 3 Sustained activation of ligand dependent c-met protein; data show that c-met amplification is closely related to resistance to EGFR inhibitors, About 3% of NSCLC patients had a jump mutation in exon 14, and about 2% had gene amplification < br / > on March 25, 2020, the world's first c-met selective inhibitor, tepmetko ® (tepotinib), was first approved for marketing in Japan The first approved indication was non-small cell lung cancer with jump mutation of exon 14 of met In 2020, ASCO also updated tepotinib data (), but it is not the focus of this article, and interested patients can view the official data in detail < br / > sym015 has a good response in met amp / exon 14 del non-small cell lung cancer patients: orr 25% < br / > < br / > < br / > sym015-01 clinical trial design < br / > < br / > < br / > sym015 has a good clinical response, 20 patients, 5 patients (25%) response < br / > < br / > < br / > sym015 is composed of two humanized IgG1 monoclonal antibodies targeting different epitopes of met, namely hu9006, hu9338 Sym015 can avoid Miss target and acquired drug resistance to some extent, and the drug can further improve the clinical benefits of patients Sym015 is a met targeted therapy worthy of attention in addition to tepotinib < br / > on May 18, 2020, the data of destiny-lung01 showed that trastuzumab deluxtecan bring significant clinical benefits to patients with advanced non-small cell lung cancer with HER2 mutation after advanced metastatic platinum chemotherapy, and FDA granted them a breakthrough treatment identification < br / > on December 20, 2019, trastuzumab deluxtecan was approved for three-line treatment of HER2 positive breast cancer patients, which is the first batch of trastuzumab deluxtecan in the world The road of drug heavyweight officially opened, and the innovation breakthrough has not stopped! < br / > < br / > < br / > < br / > amivantamab (egfrxcmet duobody ®) is an EGFR / c-Met bispecific antibody originally developed by genmab Amivantamab is a drug worthy of attention for EGFR mutation patients At the ASCO meeting in 2020, amivantamab updated the early response data of EGFR exon 20 int mutation patients Of the 50 patients, 39 were evaluable, 14 PR, and the objective response rate was 36% < br / > nct02609776 is still in progress, and the benefits of amivantamab in patients with EGFR driven gene mutations are still under evaluation < br / >, Targeted chemotherapy is also constantly bringing clinical benefits to patients with driving gene mutation The fine stratification of the population is bringing accurate treatment to patients It is worth noting that: < br / > 1 EGFR targeted treatment, EGFR exon 20 ins non-small cell lung cancer patients will usher in new programs, such as mobocertinib, double anti amivantamab; < br / > 2 KRAS targeted treatment, The patients with KRAS G12C mutation and non-small cell lung cancer will also have new breakthroughs, such as sotorasib; < br / > 3 New targeted therapy is constantly expanding and accurately mining the beneficiary population At the same time, among the patients with acquired drug-resistant mutation treated by traditional targeted therapy, the new generation of targeted therapy represented by oxitinib is innovating the clinical benefits of drug-resistant mutation patients, such as oxitinib and amivantamab.